Low Mortality and Key Aspects of Delivery of Care for End-Stage Renal Disease in Italy

End-stage renal disease (ESRD) is a global health problem. There are differences in mortality among patients with ESRD amid industrialized countries that may be related to their respective systems of delivery of care. A nationwide survey was completed in Italy, a country with low mortality rate for ESRD patients, in order to help understand key aspects of ESRD delivery of care that contribute to mortality. Survey responses were obtained and analyzed from 131 of 575 dialysis centers (23%), covering data from 13,170 dialysis patients in 2006. The mortality rate was 11.2% and the prevalence of diabetes-associated kidney disease was 21%. Of the patients, 88% were on hemodialysis and 12% were on peritoneal dialysis. Most patients were in the age range of 65–75 years (66.7%), were seen by a nephrologist at CKD stage 3, and began dialysis at mean estimated GFR of 9.6 ml/min/1.73 m2. AV fistulae were the prevailing form of vascular access (83%) and were most frequently placed by a nephrologist (61.2%). In 98% of the dialysis centers, a nephrologist was present during dialysis sessions. The following may explain the low mortality for ESRD patients in Italy: low prevalence of diabetes, high use of AV fistulae, delivery of care by nephrologists beginning in pre-ESRD stages, their involvement in placement of dialysis vascular access, and their physical presence requirement during dialysis sessions. These findings portray key aspects of the contemporary delivery of care for Italian dialysis patients and provide a platform for international comparison of healthcare systems for ESRD

Sex Differences in Cardiovascular Research: A Scientometric Analysis

Background We sought to investigate sex‐specific differences in authorship of cardiovascular research over the past decade. Methods and Results All 387 463 cardiovascular publications between 2010 and 2019 were retrieved from Web of Science. Articles increased from 19 960 to 29 604 articles per year (P>0.001). The number of articles written by female first authors increased by 76.3% (6434–11 343 articles) and by 35.0% for male first authors (13 526–18 261) (P<0.001). The first author was more likely to be a female author in articles with female last authors. The median impact factor (IF) for articles by female first authors was lower (2.46 [interquartile range, 7 1.11–4.03] versus 2.51 [interquartile range, 1.17–4.10]; P<0.001). Female authorship articles reached the highest IF in North America (average IF, 3.7), with the lowest in Africa (average IF, 1.8). Conclusions Publications in cardiovascular research have increased over the past decade, particularly by female authors. Female researchers are cited less often compared with their male peers. The IF remains lower for articles by female researchers

Aquatic-terrestrial transitions of feeding systems in vertebrates : a mechanical perspective

Transitions to terrestrial environments confront ancestrally aquatic animals with several mechanical and physiological problems owing to the different physical properties of water and air. As aquatic feeders generally make use of flows of water relative to the head to capture, transport and swallow food, it follows that morphological and behavioral changes were inevitably needed for the aquatic animals to successfully perform these functions on land. Here, we summarize the mechanical requirements of successful aquatic-to-terrestrial transitions in food capture, transport and swallowing by vertebrates and review how different taxa managed to fulfill these requirements. Amphibious ray-finned fishes show a variety of strategies to stably lift the anterior trunk, as well as to grab ground-based food with their jaws. However, they still need to return to the water for the intra-oral transport and swallowing process. Using the same mechanical perspective, the potential capabilities of some of the earliest tetrapods to perform terrestrial feeding are evaluated. Within tetrapods, the appearance of a mobile neck and a muscular and movable tongue can safely be regarded as key factors in the colonization of land away from amphibious habitats. Comparative studies on taxa including salamanders, which change from aquatic feeders as larvae to terrestrial feeders as adults, illustrate remodeling patterns in the hyobranchial system that can be linked to its drastic change in function during feeding. Yet, the precise evolutionary history in form and function of the hyolingual system leading to the origin(s) of a muscular and adhesive tongue remains unknown

CD4 + T cells recognize conserved influenza A epitopes through shared patterns of V-Gene usage and complementary biochemical features

T cell recognition of peptides presented by human leukocyte antigens (HLAs) is mediated by the highly variable T cell receptor (TCR). Despite this built-in TCR variability, individuals can mount immune responses against viral epitopes by using identical or highly related TCRs expressed on CD8+ T cells. Characterization of these TCRs has extended our understanding of the molecular mechanisms that govern the recognition of peptide-HLA. However, few examples exist for CD4+ T cells. Here, we investigate CD4+ T cell responses to the internal proteins of the influenza A virus that correlate with protective immunity. We identify five internal epitopes that are commonly recognized by CD4+ T cells in five HLA-DR1+ subjects and show conservation across viral strains and zoonotic reservoirs. TCR repertoire analysis demonstrates several shared gene usage biases underpinned by complementary biochemical features evident in a structural comparison. These epitopes are attractive targets for vaccination and other T cell therapies

Allometry and Ecology of the Bilaterian Gut Microbiome.

Classical ecology provides principles for construction and function of biological communities, but to what extent these apply to the animal-associated microbiota is just beginning to be assessed. Here, we investigated the influence of several well-known ecological principles on animal-associated microbiota by characterizing gut microbial specimens from bilaterally symmetrical animals (Bilateria) ranging from flies to whales. A rigorously vetted sample set containing 265 specimens from 64 species was assembled. Bacterial lineages were characterized by 16S rRNA gene sequencing. Previously published samples were also compared, allowing analysis of over 1,098 samples in total. A restricted number of bacterial phyla was found to account for the great majority of gut colonists. Gut microbial composition was associated with host phylogeny and diet. We identified numerous gut bacterial 16S rRNA gene sequences that diverged deeply from previously studied taxa, identifying opportunities to discover new bacterial types. The number of bacterial lineages per gut sample was positively associated with animal mass, paralleling known species-area relationships from island biogeography and implicating body size as a determinant of community stability and niche complexity. Samples from larger animals harbored greater numbers of anaerobic communities, specifying a mechanism for generating more-complex microbial environments. Predictions for species/abundance relationships from models of neutral colonization did not match the data set, pointing to alternative mechanisms such as selection of specific colonists by environmental niche. Taken together, the data suggest that niche complexity increases with gut size and that niche selection forces dominate gut community construction.IMPORTANCEThe intestinal microbiome of animals is essential for health, contributing to digestion of foods, proper immune development, inhibition of pathogen colonization, and catabolism of xenobiotic compounds. How these communities assemble and persist is just beginning to be investigated. Here we interrogated a set of gut samples from a wide range of animals to investigate the roles of selection and random processes in microbial community construction. We show that the numbers of bacterial species increased with the weight of host organisms, paralleling findings from studies of island biogeography. Communities in larger organisms tended to be more anaerobic, suggesting one mechanism for niche diversification. Nonselective processes enable specific predictions for community structure, but our samples did not match the predictions of the neutral model. Thus, these findings highlight the importance of niche selection in community construction and suggest mechanisms of niche diversification

Diffusion Tensor Imaging of Frontal Lobe in Autism Spectrum Disorder

To investigate frontal lobe white matter in children with autism spectrum disorder (ASD), we performed diffusion tensor imaging (DTI) in 50 ASD children (mean age: 57.5 ± 29.2 months, 43 males) and 16 typically developing children (mean age: 82.1 ± 41.4 months, 11 males). The apparent diffusion coefficient (ADC) was significantly higher for whole frontal lobe (P = 0.011), long (P < 0.001) and short range (P = 0.0126) association fibers in ASD group. There was a trend toward statistical significance in the fractional anisotropy (FA) of whole frontal lobe fibers (P = 0.11). FA was significantly lower in ASD group for short range fibers (P = 0.0031) but not for long range fibers (P = not significant [NS]). There was no between-group difference in the number of frontal lobe fibers (short and long) (P = NS). The fiber length distribution was significantly more positively skewed in the normal population than in the ASD group (P < 0.001). The long range association fibers of frontal lobe were significantly longer in ASD group (P = 0.026 for both left and right hemispheres). Abnormal frontal FA and ADC may be due to white matter organization abnormalities in ASD. Lack of evidence for excessive short range connectivity in ASD in this study may need to be re-examined with future advances in DTI technology

Hydrodynamics of fossil fishes

Fromtheir earliest origins, fishes have developed a suite of adaptations for locomotion in water, which determine performance and ultimately fitness. Even without data from behaviour, soft tissue and extant relatives, it is possible to infer a wealth of palaeobiological and palaeoecological information. As in extant species, aspects of gross morphology such as streamlining, fin position and tail type are optimized even in the earliest fishes, indicating similar life strategies have been present throughout their evolutionary history. As hydrodynamical studies become more sophisticated, increasingly complex fluid movement can be modelled, including vortex formation and boundary layer control. Drag-reducing riblets ornamenting the scales of fast-moving sharks have been subjected to particularly intense research, but this has not been extended to extinct forms. Riblets are a convergent adaptation seen in many Palaeozoic fishes, and probably served a similar hydrodynamic purpose. Conversely, structures which appear to increase skin friction may act as turbulisors, reducing overall dragwhile serving a protective function. Here,we examine the diverse adaptions that contribute to drag reduction in modern fishes and review the few attempts to elucidate the hydrodynamics of extinct forms

Acquisition of suppressive function by conventional T cells limits antitumor immunity upon Treg depletion

Regulatory T (Treg) cells contribute to immune homeostasis but suppress immune responses to cancer. Strategies to disrupt Treg cell–mediated cancer immunosuppression have been met with limited clinical success, but the underlying mechanisms for treatment failure are poorly understood. By modeling Treg cell–targeted immunotherapy in mice, we find that CD4+ Foxp3− conventional T (Tconv) cells acquire suppressive function upon depletion of Foxp3+ Treg cells, limiting therapeutic efficacy. Foxp3− Tconv cells within tumors adopt a Treg cell–like transcriptional profile upon ablation of Treg cells and acquire the ability to suppress T cell activation and proliferation ex vivo. Suppressive activity is enriched among CD4+ Tconv cells marked by expression of C-C motif receptor 8 (CCR8), which are found in mouse and human tumors. Upon Treg cell depletion, CCR8+ Tconv cells undergo systemic and intratumoral activation and expansion, and mediate IL-10–dependent suppression of antitumor immunity. Consequently, conditional deletion of Il10 within T cells augments antitumor immunity upon Treg cell depletion in mice, and antibody blockade of IL-10 signaling synergizes with Treg cell depletion to overcome treatment resistance. These findings reveal a secondary layer of immunosuppression by Tconv cells released upon therapeutic Treg cell depletion and suggest that broader consideration of suppressive function within the T cell lineage is required for development of effective Treg cell–targeted therapies